The basic objectives of this research project are, a) to obtain a more complete understanding of the physiological mechanisms that participate in the regulation of renal blood flow, glomerular dynamics and filtration rate, and peritubular capillary dynamics, and b) to determine more precisely the relationship of the factors that control renal hemodynamics to the overall control of sodium and water excretion. Because of its potential significance as a primary controlling system, emphasis will be placed on a detailed examination of the mechanisms responsible for the intrinsic regulation of segmental vascular resistance. As part of our "systems analysis" approach to these problems, work on a mathematical model of renal vascular and tubular hydrodynamics will be continued. Specifically, work during this project period will concentrate on a more complete evaluation of the distal tubular feedback hypothesis evoked to explain the phenomenon of renal autoregulation, one manifestation of the intrinsic mechanism that controls renal vascular resistance. The studies include whole kidney clearance and blood flow experiments and emphasize the application of micropuncture techniques to evaluate this hypothesis at the single nephron level. Distal nephron microperfusion techniques will be utilized to evaluate the role of the various candidates that have been proposed to serve as the feedback mediator, in particular sodium and calcium. Other studies will include, a) a more complete description of the segmental flow, pressure and resistance characteristics of the renal vascular and tubular networks and how these are affected by various vasoactive agents, b) investigations on the mechanism by which changes in arterial pressure cause changes in fractional water and sodium excretion (pressure diuresis), c) an evaluation of peritubular capillary and interstitial fluid dynamics governing peritubular capillary uptake, and d) a more complete description of glomerular dynamics (specifically glomerular pressure, single nephron glomerular filtration rate, and glomerular membrane permeability) in the dog.